chr8-102649991-G-A

Position:

• chr8-102649991-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005655.4(KLF10):​c.*141C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 1,092,662 control chromosomes in the GnomAD database, including 67,889 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (7657 hom., cov: 33)
  • Exomes 𝑓: 0.35 (60232 hom.)
• Consequence: KLF10 NM_005655.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.94

Genes affected

KLF10 (HGNC:11810): (KLF transcription factor 10) This gene encodes a member of a family of proteins that feature C2H2-type zinc finger domains. The encoded protein is a transcriptional repressor that acts as an effector of transforming growth factor beta signaling. Activity of this protein may inhibit the growth of cancers, particularly pancreatic cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2013]

KLF10 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 8-102649991-G-A is Benign according to our data. Variant chr8-102649991-G-A is described in ClinVar as [Benign]. Clinvar id is 1181757.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLF10	NM_005655.4	c.*141C>T		3_prime_UTR_variant	4/4	ENST00000285407.11	NP_005646.1
KLF10	NM_001032282.4	c.*141C>T		3_prime_UTR_variant	4/4		NP_001027453.1
KLF10	NR_103759.2	n.909C>T		non_coding_transcript_exon_variant	3/3
KLF10	NR_103760.2	n.1032C>T		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLF10	ENST00000285407.11	c.*141C>T		3_prime_UTR_variant	4/4	1	NM_005655.4	ENSP00000285407.6
KLF10	ENST00000395884.3	c.*141C>T		3_prime_UTR_variant	4/4	1		ENSP00000379222.3

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47193 AN: 152110 Hom.: 7655 Cov.: 33

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.311

GnomAD4 exome AF: 0.354 AC: 332761 AN: 940434 Hom.: 60232 Cov.: 12 AF XY: 0.354 AC XY: 165848 AN XY: 468608

Gnomad4 AFR exome AF: 0.243

Gnomad4 AMR exome AF: 0.285

Gnomad4 ASJ exome AF: 0.375

Gnomad4 EAS exome AF: 0.164

Gnomad4 SAS exome AF: 0.354

Gnomad4 FIN exome AF: 0.296

Gnomad4 NFE exome AF: 0.371

Gnomad4 OTH exome AF: 0.354

GnomAD4 genome AF: 0.310 AC: 47211 AN: 152228 Hom.: 7657 Cov.: 33 AF XY: 0.307 AC XY: 22813 AN XY: 74430

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.384

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.363

Gnomad4 OTH AF: 0.309

Alfa AF: 0.353 Hom.: 9360

Bravo AF: 0.306

Asia WGS AF: 0.299 AC: 1042 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	12
DANN	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3191333; hg19: chr8-103662219; COSMIC: COSV53435697;